Age-Associated KLF9 Enhances the Inflammatory Response of Alveolar Macrophages Via Regulating TLR2 Expression.

Abstract

Staphylococcus aureus pneumonia is a severe infection in infant and young children. Toll-like receptor 2 (TLR2)-mediated inflammation plays essential roles in S. aureus pneumonia. Krueppel-like factor 9 (KLF9) is a transcriptional factor participating in multiple cellular aspects including inflammation. In this study, the potential roles of KLF9 in S. aureus pneumonia were evaluated. The expression of KLF9 in peripheral blood mononuclear cells (PBMCs) from healthy donors with different ages and in alveolar macrophages from mice with different ages was measured. Pam3CK4-induced expression of inflammatory cytokines was compared in alveolar macrophages from young and old mice and in wild-type (WT) and KLF9-deficient macrophages. The survival rate, body weight loss, lung pathology were compared between WT and KLF9-deficient mice after S. aureus infection. The TLR2 expression was compared between WT and KLF9-deficient macrophages after Pam3CK4 treatment. Decreased expression of KLF9 was detected in PBMCs from elder donor and in macrophages from old mice. Impaired expression of pro-inflammatory cytokines was observed in macrophages from old mice and KLF9-deficient macrophages after Pam3CK4 treatment. KLF9-deficient mice had elevated survival rate, decreased lung injury after S. aureus infection. Decreased expression of TLR2 was detected in KLF9-deficient macrophages and overexpression of TLR2 rescued the impaired expression of inflammatory cytokines in KLF9-deficient macrophages. KLF9 regulated inflammatory responses in macrophages through TLR2.